However, individuals with intermediate thymic function (percentage of DP between 10% and 40%) also had intermediate CD4/CD8 ratios, while higher thymic function (as defined by percentage of DP higher than 40%) showed lower ratios, with similar CD4 and CD8 T cell production

However, individuals with intermediate thymic function (percentage of DP between 10% and 40%) also had intermediate CD4/CD8 ratios, while higher thymic function (as defined by percentage of DP higher than 40%) showed lower ratios, with similar CD4 and CD8 T cell production. cells could also show age-related defects. It has been reported in both, animal models and humans, alterations of the naive T cell turnover associated to advanced age or low thymic function. However, as far as we know, homeostatic mechanisms involved in the deregulation of naive T cell peripheral dynamics and their consequences are still not well understood. Thus, the aim of our study was to analyze homeostatic parameters of peripheral naive T cells and their relationship with thymic function in young and elderly humans. Our results show that lower naive T cell numbers were associated with a lower thymic function and higher activation and proliferating naive T cell levels. We then analyzed sjTREC numbers and relative telomere length from sorted naive T cells. Our results show that the aberrant activation and proliferation status was related to lower sjTREC numbers (a peripheral proliferation marker) and both, higher CD57 expression levels and shortened telomeres (replicative senescence-related markers). Elderly individuals show a greater contraction of the CD8 naive T cell numbers and all homeostatic alterations were more severe in this compartment. In addition, we found that low functional thymus show a CD4-biased thymocyte production. Taken together, our results suggest a homeostatic deregulation, affecting mostly the naive CD8 T cell subset, leading to the accumulation of PF-3274167 age-associated defects in, otherwise, phenotypically naive T cells. Electronic supplementary material The online version of this article (doi:10.1007/s11357-010-9170-8) contains supplementary material, which is available to authorized users. test was used to analyze differences between continuous variables. Statistical analysis was performed using the Statistical PF-3274167 Package for the Social Sciences software (SPSS 17.0, Chicago, IL). Results Age-related changes of the T-lymphocytes subsets Forty-four individuals were analyzed and divided in two groups ( 50 and? ?50?years) according to their ages. Characteristics of the cohort are summarized in Table?1. In the elder group, CD8 absolute counts showed a significant reduction, whereas CD4 T cells numbers were similar. CD4 and CD8 T cells were then isolated and T-lymphocyte subsets were analyzed, by flow cytometry, as shown in Fig.?1a. Percentage of effector T cells (as defined by CD4+CD27- or CD8+CD27?) was higher in the elder group, showing statistical significance in CD8 T cells (Fig.?1b). The peripheral naive to memory T cell ratio from elder individuals was decreased in both, CD4 and CD8 subsets but, once again, the contraction was PF-3274167 greater in CD8 T cells (Fig.?1c). Decrease in the naive/memory ratio could be explained by increased percentages of memory T cells but also by a naive T cell drop. In our cohort, memory T cells were not increased in elder individuals (data not shown). However, naive T cells showed a steep drop PF-3274167 with age. As expected after the SGK2 naive/memory results, the decrease was higher in the naive CD8 T PF-3274167 cell compartment (Fig.?1d). Table?1 Characteristics of the cohort test). IL-7 provides survival signals on naive T cells but animal models showed that, when IL-7-derived signal is stronger, this could lead to activation and proliferation of naive T cells (Takada and Jameson, 2009). Thus, we analyzed whether the drop in naive T cell numbers without IL-7 levels reduction could alter their homeostatic parameters. In order to check the homeostatic parameters of the naive T cell subset we analyzed activation (CD38+HLADR+), proliferating (Ki67+) and replicative senescent (CD57+) naive T cell levels in both.